Considering the overall goal of this project, which is to demonstrate the functionality of a new generation of brain implants with closed-loop neuromodulation capabilities based on graphene microelectrode technologies and a minimally invasive robotic implantation procedure for the treatment of brain disorders, the main achievements of MINIGRAPH during the first year of the project have been the following:
1) With respect to technology of epicortical and subcortical neural probes, we have designed, fabricated and characterized a first generation (polymer-only encapsulation) of graphene-based neural probes. The design (dimensions and layout of microelectrodes) considered input from end-users (clinicians and neuroscientists partners) and from electronic design partners. Furthermore, a fabrication strategy to improve hermeticity of neural leads has started based on a stack of inorganic/organic thin layers.
2) Regarding the development of the integrated electronic system to interface with the neural probes, a first version of the ASIC with recording and stimulation channels (16 independent stimulation channels and 240 recording channels) has been designed and simulated. In addition, the architecture of a non-implantable data-acquisition system to enable first in vivo experiments has been defined.
3) In the case of the implantable functional prototype that integrates the neural probes and the ASIC, we have evaluated and assessed different microfabrication strategies (at 8’ wafer scale) combining polymer and inorganic thin-film technology.
4) In the area of minimally invasive robotic surgical procedure, the requirements for the magnetic carrier and delivery system, as well as for the human-machine interface, have been identified, and an initial concept for the robotic system set-up has been defined and validated.
5) with respect to the closed-loop software for brain neuromodulation and the functional validation of the prototype in a translational model, we have first developed a porcine acute model for testing the developed devices, validating synchronized recording of animal behaviour by measuring pathological metrics, brain signals, closed-loop stimulation and therapy effects on the behavioural metrics reflecting therapy. In addition, we demonstrated a closed-loop dataflow in the porcine animal model incorporating machine learning models to close the loop with stimulation in real-time.
6) Regarding the regulatory strategy for approval of implant and implantation procedure, we have a preliminary draft of a detailed strategy & plan for biological safety verification of the manufactured, packaged, and sterilised investigational devices demonstrating compliance with applicable ISO standards.
7) Through an EU Hope on facility call, we have incorporated a partner (in July 2023) to evaluate the fundamental toxicity of neural probes on cellular and molecular level. We have already drafted a detailed plan for the in vitro cytotoxicity tests, and we have initiated the definition of prototype models for in-silico evaluation of interactions of graphene-based materials with lipid membranes.
